Mass spectrometry is now established as an essential tool in the biological research laboratory and is widely used for characterizing clinicaly significant peptides and proteins. However, more than twenty years after the advent of the enabling approaches of matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization, there has been only marginal success in the implementation of mass spectrometry in routine clinical determination of proteins. In large part, this may be attributed to the fact that t present there is no concerted enterprise that systematically tailors and produces devoted analytical platforms and matched standardized assays to meet the specifications and needs of clinical practitioners. In this project we respond to this problem by assembling pioneers in the design, production and application of MALDI-time-of-flight mass spectrometry and mass spectrometric immunoassay: two technologies that will be combined to form a Next- Generation Clinical Mass Spectrometry Platform. These team members are joined by experts in the fields of Clinical Endocrinology and Population Proteomics, whose guidance is essential in defining platform specifications and lead assays for routine clinical application, as well as for producing the data that underpin an understanding of the importance of protein diversity in the human population. In this project a cross-disciplinary Industrial and Academic team will design and build a new, dedicated high-performance mass spectrometry platform to clinical specifications, and translate it and accompanying standardized assays into tools that can be exploited in clinical research. The small business members of this team possess unique expertise, intellectual property, and facilities not only to develop the new mass spectrometry platform and assays but also to marshall the resources needed to make the results of the project commercially available in phase III. Completion of this Program will impact a Scientific Knowledge Gap (of protein microheterogeneity in human populations) aligned with numerous current and future Significant Research Opportunities in Basic and Clinical Research. Also a scalable Translational Mechanism will be created that expands beyond the initial scope of this Program and deeper into long-term clinical markets by adding more assays towards known clinically significant proteins, as well as other new candidate biomarkers. Consequently, we anticipate the increased use of our Next-Generation Clinical Mass Spectrometry Platform in clinical scenarios where standardized technologies are routinely applied toward known markers to help define pathobiology's underlying disease, the clinical status of individuals with disease, and as part of advanced workflows toward novel biomarkers stemming from numerous protein-based discovery efforts currently ongoing worldwide. PUBLIC HEALTH RELEVANCE: The Program relates to public health by producing a new, high information content tool that addresses a significant scientific knowledge gap commonly encountered in the Basic Biomedical Research and Clinical Monitoring of peptides and proteins (micro heterogeneity). Consequently, we anticipate the increased use of our Next-Generation Clinical Mass Spectrometry Platform in immediate and future clinical scenarios where standardized technologies are routinely applied toward markers to monitor the health status of individuals, to help understand pathobiology's underlying disease, and as part of workflows toward new biomarkers stemming from numerous protein-based discovery efforts currently ongoing worldwide